This invention pertains to a method for the treatment of progressive systemic sclerosis by the oral administration of finely divided animal, fish or reptilian cartilage.
Progressive systemic sclerosis (PSS) is a connective tissue disease that ultimately leads to fibrosis involving the skin (scleroderma) and widely disseminated internal organs including the gastrointestinal tract, lungs, heart, and kidney. A chronic disorder of unknown etiology, PSS is often initially identified by the appearance of tight, firm skin on the patient sometime prior to the apparent involvement of internal organs. In some patients, internal disease can occur in the absence of skin involvement. PSS is more common in women. The terms PSS, scleroderma and dermatosclerosis are used interchangeably to identify this disorder. In the advanced stages of the disease the skin becomes firm, thickened and leathery in appearance and is tightly bound to the underlying subcutaneous tissue. Taughtness of the skin over the fingers, and arms may limit full extension of these organs.
Although many drugs have been used to treat PSS, there is no known cure and no single drug has produced any prolonged consistent therapeutic benefit. An article by Prudden and Balassa in "Seminars in Arthritis and Rheumatism" (Vol. III, No. 4-Summer 1974, pp. 287-321) discloses (pp. 317-319) the administration to a patient afflicted with PSS (of a five percent (5%) solution of a sterile high termperature aqueous cartilage extract) by subcutaneous injection. In this trial the patient received between about 50 and 400 cc of the 5% extract per month. The article reports that some improvement was noted in the patient's skin flexibility and thickness, but does not indicate any significant alleviation of the limited range of motion in certain body appendages that is a common feature of the disease. Also it did not comment on any improvement or effect on gastric-intestinal function or respiratory efficiency, both of which are affected by this systematic malady. The pharmaceutical formulation used by Prudden, et al. in "Seminars in Arthritis and Rheumatism" was prepared by extracting finely divided cartilage powder under high temperature and high pressure in an autoclave. All treatment was given via the parenteral route. The patient received the equivalent of between about 21/2 and 20 grams per month of finely divided cartilage powder (in divided doses administered at spaced apart intervals) through the parenteral route. In most instances it was necessary to admit the patient to the hospital to administer the large volumes of liquid medication that were required. The article by Prudden et al suggests that parenteral administration of the active agent in a liquid dosage form is required to facilitate transport of the agent throughout the body.
The treatment disclosed in the preceding article does not lend itself to self-administration by the patient on a long term basis, utilizes a pharmaceutical formulation that is relatively expensive to prepare (due to the need for extraction at high temperature and under high pressure) and is limited to the administration of relatively low quantities (between about 21/2 and 20 grams) of active agent per month.
It has now been unexpectedly found that the limited range of joint motion associated with PSS and particularly scleroderma can be treated through the high dose oral administration of finely divided cartilage powder of the type having been previously described in U.S. Pat. No. Re. 28,093.
Accordingly, one aspect of the present invention is to provide a method of treating PSS, scleroderma and related disorders in mammals.
A further aspect of the present invention involves the treatment of PSS in mammals by the oral administration of an effective quantity of a pharmaceutical formuation containing finely divided cartilage powder.
Still another aspect of the present invention is to provide a method of improving joint mobility and alleviating skin tension in mammals afflicted with PSS by the oral administration of at least about five grams per day of finely divided cartilage powder.
These and other objects of the present invention will be apparent upon consideration of the following specification.
As used throughout the specification the term "cartilage product" means finely divided cartilage powder derived from granulated animal, reptile or fish cartilage.
The cartilage products used in the composition of the present invention are old and have been described in U.S. Pat. No. Re. 28,093, the disclosure of which is incorporated herein by reference. The cartilage used to make the cartilage products of this invention are preferably derived from young cartilage, i.e. from young animals or, young or newly regenerated cartilage
from older animals as reptiles or from species such as fish or shark in which the cartilage remains permanently young. Where age is the criteria for determining "youth", the cartilage is preferably derived from animals not over six months old. However, cartilage products made from the cartilage of older animals may also be employed, but is somewhat less effective in treating PSS.
The cartilage may be prepared by any suitable means to result in a product which is essentially pure cartilage substantially free from adhering tissue which may have been removed by acid pepsin or other suitable enzyme treatment, with or without mechanical assistance or otherwise.
The cartilage powder material of the present invention is preferably prepared by pulverizing rough granulated cartilage to an average particle size of less than about 150 microns, and preferably less than 70 microns. Any number of techniques including ball milling, hammer milling in an inert atmosphere, pebble milling and fluid energy mill grinding may be used to pulverize the cartilage materials. Further details on the preparation of the cartilage powder products that are useful in the present invention are given in U.S. Pat. No. 3,400,199. The cartilage product of the present invention should be formulated so as to be suitable for oral administration. Preferably, the active ingredient is contained in a solid dosage form such as a capsule beadlet or tablet. However, liquid suspensions, solutions, powders, gels and solutions of cartilage powder formulated for oral administration may also be used successfully. The quantity or effective dose supplied by each dosage unit (e.g. capsule or tablet) is relatively unimportant as the total dosage can be reached by administration of either one or a plurality of capsules or tablets or both. The capsules employed may be formed with any of the well-known pharmaceutically acceptable materials such as gelatin, cellulose derivatives, etc. Tablets may be formulated in accordance with conventional tableting procedures employing solid carriers and lubricants that are well known in the art. Examples of solid carriers that may be used in the present invention include starch, sugar and bentonite.
In the treatment of PSS and scleroderma in particular, the active cartilage agent is orally administered to the patient on a daily basis in relatively high dosages of between about 9 and about 60 grams per day. Preferably, the active agent is adminstered in the form of hard shell capsules or tablets containing between about 50 and 500 milligrams of the active ingredient. An especially preferred form of the invention involves administration of a hard shell dosage form containing 375 milligrams of active ingredient.
For patients suffering from PSS, the active ingredient is preferably administered at a dosage level of between 9 and about 60 grams per day. The total daily dose is preferably administered in divided dosages taken two or three times per day. The precise quantity of active ingredient to be administered to a particular patient according to this invention depends upon the severity of condition, the stage and the individual characteristics of the patient under treatment.
An unexpected benefit of the present invention is the rapid alleviation of skin tautness and increase in joint mobility experienced by patients shortly after initiation of treatment. As the onset of PSS occurs over a relatively long time period, it is especially surprising to achieve relatively rapid reversal of the principal clinical symptoms of the disease. This was particularly unexpected in view of the long gradual onset of the disease.
A further surprising aspect of the present invention is that this rapid reversal of scleroderma symptoms is achieved with a drug administered via the oral route. Especially noteworthy was the increase in range of joint motion experienced by patients receiving the drug (as this improvement is measured with an objective test).